Estudo sobre o papel da Resolvina de série D1 (RvD1) na resposta de células T CD8 de memória

Abstract

Memory CD8 T cells are responsible for infection control and are essential to vaccine and immunotherapy design. The presence of inflammation is crucial in the differentiation of these cells, however an exacerbated inflammation can prejudice the memory CD8 T cells response. The pro-resolution phase is responsible for the development of an anti-inflammatory response that involving specialized pro- resolving mediators (SPM), such as resolvins. Resolvin D1 (RvD1) is biosynthesized from DHA (docosahexaenoic acid), has anti-inflammatory activity and can modulate T cell response. In this study, we evaluated the role of RvD1 in human memory CD8 T cells in vitro and in murine CD8 T cells during a viral infection model. We used peripheral blood mononuclear cells from healthy individuals stimulated with anti- CD3/CD28 (TCR stimulation) and treated with 10nM RvD1 at different times. Results indicate that pretreatment of RvD1 expands memory cells but does not interfere in cell survival and cytotoxicity. Also, this increase of memory cells is dependent on the mTOR pathway and production of IL-12. For viral infection model, female Balb/c mice was used between 6-8 weeks of age infected with 107 PFU VSR intranasally and treated with 100ng RvD1 intraperitoneally on different treatment times. Treatment with RvD1,30 minutes before of infection, decreases virus-specific memory CD8 T in the lung. In contrast, treatment with RvD1 after seven days of infection increases the virus-specific memory CD8 T cells response in the lung. Purified lung memory cells from RvD1-treated animals express more II4, II10, and IFNγ. During challenge with RSV mice treated with RvD1 presented increased viral load in lung tissue and decreased serum IgG production. In summary, our results show RvD1 influences human and murine memory CD8 T cell response. However, RvD1 contributes to the generation of a non-protective phenotype CD8 memory T cell during RSV infection.